Synthesis of Mannich Bases Using Substituted Aromatic Alcohols with Secondary Amines: Relative Reactivityand Regioselectivity Depending on Substrates
10
0
0
전체 글
(2) Mannich : ! "#$ *
(3) †. .
(4) (2000. 10. 10 ) †. Synthesis of Mannich Bases Using Substituted Aromatic Alcohols with Secondary Amines: Relative Reactivity and Regioselectivity Depending on Substrates Ki-Whan Chi*, Yoon Soo Ahn, Tae Ho Park†, Jeong Soo Ahn, Hyun Ah Kim, and Joo Yeon Park Department of Chemistry, University of Ulsan, Ulsan 680-749, Korea † Korea Research Institute of Chemical Technology, Taejon 305-343, Korea (Received October 10, 2000). . , paraformaldehyde ! "## $%&' () *+, -.& /0 123 *+#4 !5(6, Mannich*+ 789 :; <= 5>. ?:@ Mannich*+@ *+# ABC#D -.@ EF#;G @ HIJK& @LM4 N OP>.. one-pot. ABSTRACT. One-pot Mannich reaction of substituted hydroxy aromatic compounds with secondary amines in an aprotic solvent has been studied. The results demonstrate that the relative reactivity and regioselectivity of the Mannich reaction depend on the steric hindrance of amines as well as the nucleophilicity of hydroxy aromatic rings.. . *+ >. tt phenol@ Mannich*+D #, Z# D N: <&'
(5) f8 c(6, phenol@ Mannich *+ # 3 Mannicho-& +$; : N ab O>. phenol@ Mannich*+D ABC2 (regioselective)() -@ ortho A&' 789>Y R O>.. , azacrown ether HIJK Y phenolj;IG@ Mannich*+D , azacrown ether G paraformaldehyde methanol$%&' *+, N,N'-(methoxymethyl)-substituted azacrown ether , N-methoxymethyl ZI& 2 -.4 *+, Mannicho- nY ¡ #\ 4 = 3. *+D Q# RS & TUV W- XY Z[ #\() ]^_` Na b c(6, TUVW d&' e#fY g -g G g -. XD hi j- @ # Mannich*+ k2() =$ j>. lm, @ TUVW *+() n8S Mannich o-Y TU pq rs Rt >0 u$-) vw xy O>Y Jz {|& @}~, , @ #& % j$ ZI) +$f? O>. s. j) I Q# q& 4 Rt? OY j - &w α- TUVW *+D T) Mannich. 1. 2. 4. 5. 6. 7. 51.
(6)
(7) . 52. $5>. ¢s£ ¤¥& Chi ¦D benzene$%&' 1,4,10,13-tetraoxa-7,16-diazacyclodecane paraformaldehyde, phenolj;I one-pot() *+, ZI@ q: §, "¨ ©ª diazacrown ether «D ¬ ) nP>.
(8) &'Y, s one-pot Mannich*+@ j $# +$#4 ®3? rs Rt N¯°, ± ² phenol@ g ³ £R . ³) hydroxypyridine, phenol& x ´ 3 Vµ -R ¶8 OY methoxyphenol, ´@ orthoAR phenolj;I, ´@ - Y , benzene?:R f8 πxR ·p ¦ , paraformaldehyde ! "## $%&' one-pot() *+, -.& /0 123 *+# ABC# 4 ?¸5>. rs Rt N¯° p¹R º azacrown ether@ Mannich*+&' @ HIJK kR *+#& TY »& ¼' N ½¾>.. Table 1. Aminomethylation of hydroxypyridines with secondary amines Substrate Amine 1 2. Isolated Temp. Solvent n Yield o ( C) (%). Product 3~7. 8. . @ #& =$ } D Aldrich=@ ~4 dt ¿? ¢) =$ 5>. chromatography@ x´$%) =$ methanol, ethyl acetate, hexaneD =$ Àx& Ár =$ 5>. TLC Â(60 F , 20 cmÃ20 cm)D Merck= ~4 =$5>. Column chromatographyY silica gel(230Ä400 mesh)4 =$Å(6, x´ÆD } 2%@ triethylamine4 ÇRr Q#4 È5>. 2ÉB ÊËÌÍD Mattson-5000(UNICAM) FT-IR 4 $r ÎÏ; Ðd5>. ÑYz ÐdD Aldrich=@ MELT TEMP Ò $5(6, Ó;¡ Y ½dt ¿¾>. H NMR(300 MHz, 200 MHz) C NMR ÊËÌÍ(75.48 MHz)D Varian Unity plus 300 FT-NMR Bruker AM-300 NMR spectrometer $r nP>. .Ô ÊËÌÍD KRATOS Profile HV-3 D Shimadzu GCMS-QP 5050 (70 eV) spectrometer $r nP>.
(9) . Table 1~6& Õ *+ @ Ô !) 1.0 mmole@ -., , paraformaldehyde 1Ó&' j-$%&(10 mL) RÅ>. *+. 1a. 2a. 3 1. 93. 80 benzene. 1a. 2b. 4 1. 90. 80 benzene. 1. 46. 80 benzene. 1b. 2a. 5 2. 15. 120 p-xylene. 1. 1b. 2a. 6. 20. 80 benzene. 2. 50. 120 p-xylene. 1b. 2b. 7 1. 56. 80 benzene. Table 2. Aminomethylation of methoxyphenols with morpholine SubstrateAmine 1 2. 1d. 2a. 1d. 2a. 1e. 2a. 254. Product 8~12. Isolated n Yield Temp. Solvent (%) (oC) 1 74 25 benzene 89 80 benzene 8 2 69 25 benzene 82 80 benzene 1 15 25 benzene 10 80 benzene 9 2 23 25 benzene 17 80 benzene 1. 0. 25 benzene. 1. 63. 80 benzene. 1 1 11 2 2 3 1 1 12 2 2 3. 82 78 77 53 0 11 19 21 36 95. 25 80 25 80 120 25 80 25 80 120. 10. 1. 13. 1f. 2a. 1f. 2a. benzene benzene benzene p-xylene p-xylene benzene benzene benzene p-xylene p-xylene. Journal of the Korean Chemical Society.
(10) ! "#$ Mannich%&' (): &*+ ,- ./01 23) 456). 53. Table 3. Aminomethylation of 2,6-disubstituted phenols with secondary amines n. Isolated Yield (%). Temp. (oC). Solvent. 13. 1. 94. 80. benzene. 2c. 14. 1. 99. 80. benzene. 1h. 2a. 15. 1. 50. 80. benzene. 1h. 2c. 16. 1. 74. 80. benzene. 1. 75. 115. n-buthanol. 1. 0. 80. benzene. 1. 0. 80. ethanol. 1. 85. 115. n-buthanol. 1. 19. 80. ethanol. 1. 9. 80. benzene. 1. 13. 80. benzene. Substrate 1. Amine 2. 1g. 2a. 1g. 1i. Product 13~20. 2a. 17. 1i. 2c. 18. 1j. 2a. 19. 1j. 2c. 20. Ö 4 1Ó Y Á <&' 18-22 _` 8× ØÙ&' $% r crude # 4 nP(6, column chromatography\4 =$¼' q :Údr Û # 4 nP>. n8S # D IR, NMR, mass spectrometer¦@ qÜ-=$r ®35>. 3-Hydroxy-2-(4'-morpholinylmethyl)pyridine(3).
(11) .. light yellow solid; mp 94-95 oC; IR(cm−1) 1. 3445, 3027, 1573, 1110, 863; H NMR(CDCl 3, 300. 139.96, 141.58, 153.85; MS m/z(rel. intensity) 194 (M+, 4), 192(60), 161(33), 133(75), 109(85), 85(77), 79(100), 66(82), 54(90)..
(12). 3-Hydroxy-2-(1'-pyrrolidinylmethyl)pyridine(4). .. colorless liquid; IR(cm−1) 3425, 2973, 2838,. 1576, 1273, 1449, 1102, 802; 1H NMR(CDCl3, 300 MHz) δ1.83(m, 4H), 2.63(m, 4H), 3.99(s, 2H), 7.03 (m, 2H), 7.95(m, 1H), 10.65(s, 1H);. 13. C NMR. (CDCl3, 75.48 MHz) 23.61, 53.59, 60.90, 122.76,. MHz) δ2.64(m, 4H), 3.75(m, 4H), 3.93(s, 2H), 7.12. 123.39, 139.45, 143.12, 154.48; MS m/z(rel. inten-. (m, 2H), 8.04(m, 1H), 10.62(s, 1H); 13C NMR(CDCl3,. sity) 178(M+, 5), 109(100), 84(15), 70(30).. 75.48 MHz) 52.81, 63.81, 66.39, 122.84, 123.55, 2001, Vol. 45, No. 1.
(13). 4-Hydroxy-2-(4'-morpholinylmethyl)pyridine(5).
(14)
(15) . 54. Table 4. Aminomethylation of various dihydroxyphenols with secondary amines Substrate Amine 1 2. 1k. 1l. 1l. 1m. 1n. Isolated Temp. n Yield o Solvent ( C) (%). Product 21~27. 2a. 21 2. 2a. 22 2. 2c. 23 2. 2a. 24 2. 2a. 25 1. 45. 89. 86. 81. 25. Table 5. Aminomethylation of fused aromatic rings with secondary amines Substrate Amine 1 2. Isolated Temp. Solvent n Yield o ( C) (%). Product 28~33. 1p. 2a. 28 1. 95. 80 benzene. 1p. 2c. 29 1. 98. 80 benzene. 71. 80 benzene. 1q. 2a. 30 1 99. 80 ethanol. 80 benzene. 80 benzene. 80 benzene. 1r. 2a. 31 1. 99. 80 benzene. 1s. 2a. 32 1. 99. 80 benzene. 1t. 2a. 33 1. 70. 80 benzene. 80 benzene. 80 benzene. MHz) δ23.55, 53.57, 55.30, 112.35, 119.92, 146.35, 148.16, 167.18; MS m/z(rel. intensity) 179(M++1, 27), 1n. 2b. 26 1. 51. 80 benzene. 178(M+, 100), 14(22), 135(12), 108(61), 84(79), 70 (91), 563(27), 47(16). 4-Hydroxy-3,5-bis(4'-morpholinylmethyl)pyridine(7). 1o. 2a. 27 1. 76. 80 benzene.
(16) . white solid; mp 173-174. o. C; IR(cm−1) 3435,. 3059, 2850, 1642, 1559, 1499, 1271, 1116, 865, 768;. . light yellow liquid; IR(cm. 1 −1. H NMR(CDCl3, 300 MHz) δ2.54(m, 8H), 3.63. ) 3415, 3244, 1922,. (s, 4H), 3.74(t, J=4.5 Hz, 8H), 8.20(m, 2H); 13C NMR. 1641, 1393, 1530, 1114, 836; 1H NMR(CDCl3, 300. (CD3OD, 75.48 MHz) δ54.54, 55.41, 67.71, 124.94,. MHz) δ2.53 (t, J=4.1 Hz, 4H), 3.57(s, 2H), 3.70. 138.96, 178.92; MS m/z(rel. intensity) 294(M++1, 14),. (t, J=4.5 Hz, 4H), 6.56(d, J=6.3 Hz, 1H), 7.91(m, 2H);. 293(M+, 46), 264(13), 235(45), 206(100), 177(35),. 13. C NMR(CD 3OD, 75.48 MHz) δ54.54, 55.25,. 67.77, 117.93, 126.16, 139.05, 139.52, 180.42; MS +. m/z(rel. intensity) 194(M , 78), 163(31), 135(35),. −1. ) 3430, 1394, 1641,. 1. 1168, 836, 547; H NMR(CDCl3/CD 3OD, 300 MHz) 1.72(m, 4H), δ2.54(m, 4H), 3.59(s, 2H), 6.43(d, J= 6.5 Hz, 1H), 7.72(m, 2H);. . white solid; mp 58-59 C; IR(cm o. −1. ) 3460, 2956,. 2834, 1619, 1584, 1153, 1110; H NMR(CDCl3, 200. 4-Hydroxy-2-(1'-pyrrolidinylmethyl)pyridine(6). 13.
(17). 3-Methoxy-6-(4'-morpholinylmethyl)phenol(8) 1. 108(100), 84(75), 56(22), 47(18)..
(18) . reddish liquid; IR(cm. 148(55), 121(65), 86(64), 66(39), 56(47).. C NMR(CDCl3, 75.48. MHz) δ2.53(m, 4H), 3.63(s, 2H), 3.70(s, 3H), 3.74 (m, 4H), 6.31(m, 2H), 6.85(s, 1H); MS m/z(rel. intensity) 223(M+, 100), 138(19), 137(57), 86(38), 57(18). 3-Methoxy-4,6-bis(4'-morpholinylmethyl)phenol(9).
(19) . colorless liquid; IR(cm. −1. ) 2950, 2840, 1460,. Journal of the Korean Chemical Society.
(20) ! "#$ Mannich%&' (): &*+ ,- ./01 23) 456) Table 6. Aminomethylation of various aromatic compounds with azacrown ethers SubstrateAmine 1 2. Isolated Temp. Solvent n Yield o ( C) (%). Product 34~39.
(21) . colorless liquid; IR(cm. (12). −1. 55. ) 3456, 2944,. 2839, 1609, 1445, 1203, 1104, 853;. 1. H NMR. (CDCl3, 200 MHz) δ2.56(t, J=4.6 Hz, 8H), 3.68 (s, 4H), 3.72(t, J=4.6 Hz, 8H), 3.77(s, 6H), 6.01 (s, 1H); MS m/z(rel. intensity) 352(M+, 19), 265(68),. 1a. 2d. 34 1. 17. 80 benzene. 208(23), 180(82), 179(100), 100(48), 56(43). o. 1 1d. 2d. 49.
(22). 2,6-Dichloro-4-(4'-morpholinylmethyl)phenol(13). . white solid; mp 86-88 C; IR(cm. −1. ) 3341, 2865,. 25 benzene. 2795, 1488, 1455, 1293, 1105, 858, 785;. NMR(CDCl3, 200 MHz) δ2.43(t, J=4.8 Hz, 4H),. 35. 1. H. 1. 59. 80 benzene. 0.5. 41. 25 benzene. m/z(rel. intensity) 261(M+, 23), 177(40), 175(65),. 0.5 60. 80 benzene. 86(100), 75(33), 56(52), 42(37).. 3.38(s, 2H), 3.71(t, J=4.8 Hz, 4H), 7.24(s, 2H); MS 1d. 2e. 36. 2,6-Dichloro-4-(4'-methyl-1'-piperazinylmethyl)phenol 1f. 2d. 37 1. 28. 80 benzene.
(23) . colorless liquid; IR(cm. (14). −1. ) 3413, 2942,. 2807, 1642, 1466, 1399, 1348, 1283, 780; 1H NMR (CDCl3, 200 MHz) δ2.34(s, 3H), 2.53(m, 8H), 3.33. 1h. 2e. 38 0.5 75. 80 benzene. (s, 2H), 7.12(s, 2H); MS m/z(rel. intensity) 276 (M++1, 17), 274(M +-1, 21), 175(32), 99(54), 75(34), 56(57), 42(100).. 1p. 2d. 39 1. 12. 80 benzene.
(24). 2,6-Dimethyl-4-(4'-morpholinylmethyl)phenol(15). . yellow liquid; IR(cm. −1. ) 3451, 3391, 2862, 2963,. 1652, 1213, 1156, 1018; 1H NMR(CD3OD, 300 MHz) δ2.17(s, 6H), 2.33(t, J=4.5 Hz, 4H), 3.33(s, 2H), 1040; H NMR(CDCl3, 200 MHz) δ2.60(t, J=4.8. 3.59(t, J=4.7 Hz, 4H), 6.82(m, 2H);. Hz, 8H), 3.59(s, 4H), 3.65(s, 3H), 3.75(t, J=4.8 Hz,. (CD3OD, 75.48 MHz) δ16.69, 54.49, 64.05, 67.87,. 8H), 6.39(s, 1H), 6.99(s, 1H); MS m/z(rel. intensity). 125.4, 128.6, 130.9, 153.7; MS m/z(rel. intensity). 322(M+, 20), 236(100), 151(21), 86(28), 56(24), 42(21)..
(25). 221(M+, 12), 218(75), 188(70), 146(78), 134(99), 99. liquid; IR(cm ) 3078, 2893, 1615,. 2,6-Dimethyl-4-(4'-methyl-1'-piperazinylmethyl)phenol. 1. 4-Methoxy-2-(4'-morpholinylmethyl)phenol(10). . colorless. −1. 1. 13. C NMR. (79), 85(100), 76(75), 55(91)..
(26) . colorless liquid; IR(cm. −1. 1519, 1469, 1352, 1289, 1106, 954; H NMR (CDCl3,. (16). 200 MHz) δ2.55(t, J=4.2 Hz, 4H), 3.65(s, 2H), 3.72. 2802, 1635, 1516, 1484, 1453, 1343, 1277, 1216, 1143,. (s, 3H), 3.74(t, J=4.8 Hz, 4H), 6.56(s, 1H), 6.74. 997, 871, 809; 1H NMR(CDCl3, 200 MHz) 2.17. +. (m, 2H); MS m/z(rel. intensity) 224 (M +1, 22), 223 +. 3,5-Dimethoxy-2-(4'-morpholinylmethyl)phenol(11).
(27) . white solid; mp 61-62 C; IR(cm o. 1. −1. ) 2957,. H NMR(CDCl3,. 200 MHz) δ2.56(m, 4H), 3.71(s, 2H), 3.73(s, 6H), 3.74(m, 4H), 6.03(m, 2H); MS m/z(rel. intensity) +. 253(M , 100), 167(89), 137(36), 109(27), 86(43), 56(19). 3,5-Dimethoxy-2,6-bis(4'-morpholinylmethyl)phenol 2001, Vol. 45, No. 1. (s, 6H), δ2.27(s, 3H), 2.49(m, 8H), 3.35(s, 2H), 6.85(s, 2H); MS m/z(rel. intensity) 234(M+, 100), 176(33),. (M , 100), 136(16), 86(22), 56(12).. 2831, 2672, 1617, 1386, 1138;. ) 3391, 2936,. 163(54), 148(43), 135(67), 99(54), 84(37), 56(53), 43(35). 2,6-Di-t-butyl-4-(4'-morpholinylmethyl)phenol(17). . white.
(28). solid; mp 88-89 oC; IR(cm−1) 3600, 2967,. 2865, 2804, 1428, 1353, 1304, 1256, 1106, 1003, 882; 1. H NMR(CDCl3, 200 MHz) δ1.45(s, 18H), 2.44. (t, J=4.5 Hz, 4H), 3.42(s, 2H), 3.73(t, J=4.4 Hz, 4H), 7.09(s, 2H); MS m/z(rel. intensity) 305(M+, 100), 248.
(29)
(30) . 56. 58(100).. (10), 219(95), 203(20), 163 (36), 164(70), 86(10). 2,6-Di-t-butyl-4-(4'-methyl-1'-piperazinylmethyl).
(31) . yellow solid; mp 84-85 C; IR(cm. −1. o. phenol(18). ). 2,3-Dihydroxy-1,4-bis(4'-morpholinylmethyl)naphth-.
(32) . colorless liquid;. alene(24). 1. H NMR(CD 3OD,. 3575, 2929, 2775, 1431, 1328, 1144, 1094, 984, 856,. 300 MHz) δ2.51(m, 8H), 3.57(m, 8H), 3.98(s, 4H),. 799; 1H NMR(CDCl3, 200 MHz) δ1.44(s, 18H), 2.23. 7.18(m, 2H), 7.80(m, 2H);. (s, 3H), 2.48(m, 8H), 3.46(s, 2H), 7.07(s, 2H); MS. MHz) δ54.51, 56.37, 67.99, 113.55, 124.07, 124.53,. m/z(rel. intensity) 318(M+, 100), 259(44), 247(61),. 129.28, 147.58; MS m/z(rel. intensity) 358(M +, 7),. 219(35), 190(17), 99(33).. 356(27), 269(73), 217(26), 182(94), 154(87), 127(100),. 2,6-Dimethoxy-4-(4'-morpholinylmethyl)phenol(19).
(33) . light yellow liquid; IR(cm. −1. ) 2947, 2839,. 1. 1610, 1516, 1460, 1220, 1113, 865; H NMR(CDCl3, 200 MHz) δ2.46(t, J=4.8 Hz, 4H), 3.44(s, 2H), 3.72 (t, J=4.8 Hz, 4H), 3.86(s, 6H), 6.57(s, 2H); MS m/z +. 13. C NMR(CD3OD, 75.48. 86(60), 59(75). 2,3-Dihydroxy-4-(4'-morpholinylmethyl)pyridine(25).
(34) . gray solid; mp 220-221 C; IR(cm o. −1. ) 3285,. 3129, 2952, 2818, 1669, 1461, 1298, 1199, 1114, 868, 677; 1H NMR(CD3OD, 300 MHz) δ2.52(t, J=. (rel. intensity) 253(M , 88), 168(100), 100(33), 86(58),. 4.5 Hz, 4H), 3.56(s, 2H), 3.69(t, J=4.7 Hz, 4H),. 56(31), 42(12).. 6.26(d, J=6.8 Hz, 1H), 6.87(d, J=6.8 Hz, 1H);. 2,6-Dimethoxy-4-(4'-methyl-1'-piperazinylmethyl).
(35) . brown liquid; IR(cm. phenol(20). −1. 13. C. NMR(CD3OD, 75.48 MHz) δ52.90, 57.25, 66.31,. ) 3426, 2932,. 108.43, 122.75, 126.18, 145.74, 158.35; MS m/z(rel.. 2800, 1507, 1454, 1277, 1108; H NMR(CDCl3, 200. intensity) 210(M+, 7), 208(M+-2, 77), 147(74), 124(93),. MHz) δ2.29(s, 3H), 2.47(m, 8H), 3.42(s, 2H), 3.87. 85(96), 56(100).. 1. (s, 6H), 6.56(s, 2H); MS m/z(rel. intensity) 266(M+, 52), 195(46), 167(55), 99(80), 70(61), 56(100), 42(65). 2,5-Bis(4'-morpholinylmethyl)hydroquinone(21).
(36). . brown solid; mp 188-191 C; IR(cm ) 3518, 3479, o. -1. 1. 2,3-Dihydroxy-4-(1'-pyrrolidinylmethyl)pyridine(26).
(37) . white solid; mp 146-147 C; IR(cm o. −1. ) 3285,. 1. 2920, 2550, 1669, 1351, 1197, 783; H NMR(CDCl3, 300 MHz) δ1.69(m, 4H), 2.48(m, 4H), 3.54(s, 2H), 13. 2961, 2841, 1455, 1021, 1654, 1233; H NMR(CD3OD,. 5.84(d, J=6.7 Hz, 1H), 6.69(d, J=6.7 Hz, 1H);. 300 MHz) δ2.39(m, 8H), 3.47(s, 4H), 3.56(m, 8H),. NMR(CDCl3, 75.48 MHz) δ23.21, 53.40, 56.20,. C NMR(CD 3OD, 75.48 MHz) δ54.53,. 106.82, 122.87, 125.73, 146.31, 158.85; MS m/z(rel.. 6.44(s, 2H);. 13. 61.19, 67.99, 117.76, 123.13, 150.84; MS m/z(rel. inten+. +. sity) 445(M +1, 5), 444(M , 18), 351(8), 277(35),. C. intensity) 194(M+, 12), 125(71), 84(30), 70(100), 60(19)..
(38). 3-Methoxy-6-(4'-morpholinylmethyl)catecol(27). 219(45), 165(27), 147(59), 113(48), 96(73), 82(75),. .. 71(92), 5(100).. 3352, 2973, 2844, 1620, 1461, 1338, 1208, 1106, 1074,. 2-Methyl-4,6-bis(4'-morpholinylmethyl)resorcinol (22).
(39) . white solid; mp 193-195 C; IR(cm o. −1. ). 1. −1. o. white solid; mp 124-125 C; IR(cm ) 3416,. 852; 1H NMR(CDCl3, 300 MHz) δ2.56(t, J=6.0 Hz, 4H), 3.66(s, 2H), 3.73(t, J=6.9 Hz, 4H), 3.84(s, 3H),. 3453, 2954, 2825, 1623, 1114; H NMR(CDCl3, 300. 6.35(d, J=12.9 Hz, 1H), 6.67(d, J=12.6 Hz, 1H); MS. MHz) δ2.1(s, 3H), 2.53(m, 8H), 3.57(s, 4H), 3.73. m/z(rel. intensity) 239(M+, 100), 153(81), 152(99),. (t, J=6.6 Hz, 8H), 6.43(s, 2H); MS m/z(rel. intensity). 138(27), 134(48), 106(36), 88(93), 86(38), 57(23).. 322(M+, 48), 235(100), 149(26), 121(12), 86(50), 57(34). 2-Methyl-4,6-bis(4'-methyl-1'-piperazinylmethyl).
(40) . light brown solid; mp 144-145 C; o. resorcinol(23).
(41). 4-Hydroxy-3-(4'-morpholinylmethyl)quinoline(28). . yellow solid; mp 78-80. o. −1. C; IR(cm ) 3454, 3063,. 2922, 2854, 1623, 1581, 1518; 1H NMR(CDCl3, 300. IR(cm−1) 3453, 2938, 2834, 1618, 1458, 1342; 1H NMR. MHz) δ2.51(t, J=6.7 Hz, 4H), 3.50(s, 2H), 3.64(t, J=8.2. (CDCl3, 300 MHz) δ2.1(s, 3H), 2.3(s, 6H), 2.37-2.65. Hz, 4H), 7.34(m, 1H), 7.61(m, 2H), 8.03(s, 1H),. (m, 16H), 3.58(s, 4H), 6.43(s, 1H); MS m/z(rel.. 8.38(m, 1H); MS m/z(rel. intensity) 245(M++1, 15),. +. intensity) 348(M , 30), 248(78), 177(15), 99(70), 70(32),. 244(M+, 100), 171(10), 158(90), 130 (26), 102(34), Journal of the Korean Chemical Society.
(42) ! "#$ Mannich%&' (): &*+ ,- ./01 23) 456). 70.54, 71.12, 123.99, 139.12, 139.66, 154.57, 207.11;. 87(74), 77(27), 57(84). 4-Hydroxy-3-(4'-methyl-1'-piperazinylmethyl).
(43) . white. quinoline(29) −1. 57. solid; mp 213-214 oC;. IR(cm ) 3450, 2943, 2789, 1623, 1571, 1501; 1H NMR(MeOH, 300 MHz) δ2.21(s, 3H), 2.51(m, 8H), 3.58(s, 2H), 7.38-8.34(m, 5H); MS m/z(rel. intensity). MS m/z(rel. intensity) 370(M +, 8), 309(3), 262(100), 232(8), 176(10), 109(64), 56(18), 45(20). 3-Methoxy-6-[(1',4',7',10',13'-pentaoxa-16'-azacy-.
(44) . colorless. clooctadecan-16'-yl)methyl]phenol(35) −1. liquid; IR(cm ) 3167, 2898, 1572, 1462, 1350, 1294,. 257(M , 55), 186(32), 171(10), 158(44), 130(14), 99(50),. 1102; 1H NMR (CDCl3, 300 MHz) δ3.60-3.75(m,. 77(19), 58(100).. 29H), 6.30(1H), 6.4(1H), 6.83(1H); MS m/z(rel. intensity). +.
(45). 8-Hydroxy-7-(4'-morpholinylmethyl)quinoline(30). . dark. −1. brown liquid; IR(cm ) 3363, 3067, 2954,. 2854, 1115; H NMR(CDCl3, 300 MHz) δ2.62 (t, 1. J=6.6 Hz, 4H), 3.77(t, J=7.1 Hz, 4H), 3.87(s, 2H),. 399(M+, 0.9), 205(21), 137(18), 86(80), 72(33), 56(56), 43(100). 7,16-Bis-[(4'-methoxyl-2'-hydroxyphenyl)methyl]-.
(46) .. 1,4,10,13-tetraoxa-7,16-diaza-cyclooctadecane(36) −1. o. 7.28(m, 2H), 7.38(m, 1H), 8.09(m, 1H), 8.85. white solid; mp 80-81 C; IR(cm ) 2937, 2852,. (m, 1H); MS m/z(rel. intensity) 244(M+, 3), 186(11),. 1616, 1453, 1196, 1102; 1H NMR(CDCl3, 300 MHz). 171(14), 159(100), 130(21), 84(55), 77(19), 56 (9).. δ2.82(t, J=5.4 Hz, 8H), 3.59(s, 8H), 3.64(t, J=5.4.
(47) .. 2-(4'-Morpholinylmethyl)-1-naphthol(31). Hz, 8H), 3.72(s, 4H), 3.74(s, 6H), 6.31(d, J= 2.5. H NMR(CDCl3, 300 MHz) δ2.6. Hz, 2H), 6.38(d, J=2.5 Hz, 2H), 6.82(d, J=8.3 Hz,. (m, 4H), 3.76(t, J=7.0 Hz, 4H), 3.82(s, 2H),. 2H); MS m/z(rel. intensity) 398(0.5), 261(27),. 7.05(m, 1H), 7.29(m, 1H), 7.44(m, 2H), 7.74(m, 1H),. 194(21), 132(98), 148(49), 87(22), 74(74), 56(95),. 8.23(1H); MS m/z(rel. intensity) 244(M ++1, 33),. 44(100).. 1. reddish liquid;. +. 243(M , 97), 170 (15), 157(55), 128(67), 102(20), 86(100), 77(22), 57(99)..
(48) .. 1-(4'-Morpholinylmethyl)-2-naphthol(32). white solid; mp 113-115 oC; IR(cm−1) 3455, 3061,. 3,5-Dimethoxy-2-[(1',4',7',10',13'-pentaoxa-16'-.
(49) .. azacyclooctadecan-16'-yl)methyl]phenol(37) −1. colorless liquid; IR(cm ) 2882, 1590, 1454, 1351, 1109, 946; 1H NMR(CDCl3, 200 MHz) δ3.57-3.85(m, 32H),. H NMR(CDCl3, 300 MHz) δ2.68. 5.97(d, 1H), 6.05(d, 1H); MS m/z(rel. intensity) 264. (s, 4H), 3.8(t, J=6.9 Hz, 4H), 4.16(s, 2H), 7.09(m, 1H),. (10), 262(5), 232(11), 204(9), 166(5), 87(22), 74(27),. 7.30(m, 1H), 7.45(m, 1H), 7.76(m, 3H); MS m/z. 56(63), 45(100).. 2959, 1116;. 1. (rel. intensity) 244(M++1, 13), 243(M+, 70), 170(7), 157(56), 128(85), 86(100), 57(90). 4-Chloro-2-(4'-morpholinylmethyl)-1-naphthol(33).
(50) . reddish liquid; IR(cm. 7,16-Bis[(3',5'-dimethyl-4'-hydroxyphenyl)methyl]-.
(51) .. 1,4,10,13-tetraoxa-7,16-diazacyclooctadecane(38) o. −1. white solid; mp 100-102 C; IR(cm ) 3466, 3209,. ) 3397, 3048, 2980,. 1668, 1224; 1H NMR(CD3OD, 300 MHz) δ2.25 (m,. 1117; H NMR(CDCl3, 300 MHz) δ2.59(m, 4H),. 12H), 2.83(t, J=6.0 Hz, 8H), 3.52(s, 4H), 3.64-3.69. 3.76(m, 6H), 7.16(s, 1H), 7.53(m, 2H), 8.19(m, 2H);. (m, 16H), 6.94(m, 4H); 13C NMR(CD3OD, 75.49 MHz). −1. 1. MS m/z(rel. intensity) 277(M , 79), 279(M +2, 47),. δ10.68, 48.83, 54.72, 64.85, 65.76, 119.56, 124.58, 125.14,. 190(60), 162(44), 127(56), 101(31), 87(100), 77(34),. 147.4; MS m/z(rel. intensity) 530 (M+, 1), 425(10), 397. 57(91).. (48), 291(51), 263(98), 163(45), 135(100), 91(5).. +. +. 3-Hydroxy-2-[(1',4',7',10',13'-pentaoxa-16'-azacyclooctadecan-16'-yl)methyl]pyridine(34) −1.
(52) .. brown 1. 4-Hydroxy-3-[(1',4',7',10',13'-pentaoxa-16'-azacy-.
(53) . white. clooctadecan-16'-yl)methyl]quinoline(39) o. −1. liquid; IR(cm ) 3436, 2955, 2851, 1573, 1418; H. solid; mp 129-131 C; IR(cm ) 3454, 2885, 1623, 1573,. NMR(CD 3OD, 300 MHz) δ2.69(m, 4H), 3.44-3.76. 1493; 1H NMR(CDCl3, 300 MHz) δ2.73(m, 4H), 3.55. 13. C NMR. (m, 22H), 7.24-8.47(m, 5H); MS m/z(rel. intensity). (CDCl3, 75.48 MHz) δ54.12, 69.75, 70.11, 70.40, 70.48,. 420(M+, 1), 418(1), 302(70), 232(10), 159(100), 145. (m, 22H), 7.01(m, 2H), 7.78(m, 1H);. 2001, Vol. 45, No. 1.
(54)
(55) . 58. (52), 130(98), 102(34), 89 (50), 77(44), 58(94).. >"w , paraformaldehyde ! "## $%&' one-pot() *+, -.& /0 123 *+#4 !5>(Scheme 1). -.@ ÝÁ& /0 Þß X Table 1Ä5& £àáP(6, Table 6D ( ) azacrown ether =$ Þß X â5>. Hydroxypyridine . phenol?: ã@ ´@ g ³R . ³) hydroxypyridine@ Mannich*+ X Table 1& £àáP>. Pyridine?: ã& OY . ³Y g ³½> x- ä#;R å', æ phenol@ paraA& x i -Y u$-R OY ç ! è éê 4 >. çD pyridine?: á@ π-x ë; Ø , hydroxypyridine@ EF#;R ì8 8 phenol½> Mannich*+& *+# í4 ç() ±ÐfP>. ¢s£ Table 1&' N Oî, 3-hydroxypyridine(1a)@ TUVW Y $w Sïf8 «D ¬) Mannich *+ 34 nP>. # 3@ H NMR ÊËÌÍ4 ð½², ¹:ñ ?:á@ ò ') ') ótô(coupling)? O(6, 9. 1. )õ *+ 789 :R -@ ortho A Z&'; ö÷)?:@ . G R øù4 ®3 ê OP>. 4-Hydroxypyridine(1b) morphorine@ Mannich*+() # 5 46%@ ¬) nP(6, D *+<&' () pyrrolidine4 =$¼ ; @ !è X nP>. , TUVW * +4 ú *hû ü2(), ÁY p-xylene&'. Ô@ 1bG Ô@ paraformaldehyde, morphorine 4 *+ý X íD ¬) # 6(50%)4 nP (6, TUVW *+ ú ï¼S # (15%) ; ®3fP>. 2-Hydroxypyridine(1c)D þÿ23 u$Y 1a, 1bG *+# j=ê ç() ±ÐfPt, D *+ <&' 1cY Mannich*+ Sïft ¿¾>. $% ethanol, p-xylene() 8; D X n PY, Y 1cR Þ)Y âé2() `d. ketoe) pq L- {|7 ç()  >. Methoxyphenol . 7*2() phenolj;I -.) =$ one-pot Mannich*+&' ú TUVW R Sï ±Y ¿>. }, phenol& x ´ u$-3 Vµ -R methoxyphenol4 -.) =$ >² -.@ D EF#() 3r íD Ó;&'; T UVW R ú Sïy ç() ±1fP>. Þß X(Table 2), Ô@ 3-methoxyphenol. 1 a 3-hydroxypyridine b 4-hydroxypyridine c 2-hydroxypyridine d 3-methoxyphenol e 4-methoxyphenol f 3,5-dimethoxyphenol g 2,6-dichlorophenol h 2,6-dimethylphenol i 2,6-di-t-butylphenol j 2,6-dimethoxyphenol k hydroquinone. 2 l 2-methylresorcinol m 2,3-dihydroxynaphthalene n 2,3-dihydroxypyridine o 3-methoxycatecol p 4-hydroxyquinoline q 8-hydroxyquinoline r 1-naphthol s 2-naphthol t 4-chloro-1-naphthol. a morpholine b pyrrolidine c N-methylpiperazine d 1,4,7,10,13-pentaoxa-16 -azacyclooctadecane e 1,4,10,13-tetraoxa-7,16 -diazacyclooctadecane. Scheme 1. Journal of the Korean Chemical Society.
(56) ! "#$ Mannich%&' (): &*+ ,- ./01 23) 456). D Ô@ morphorine, paraformaldehyde *+, ú TUVW # 8 ú TUVW # 9 nP>. *+ @ Ô =$Å4 {G Ô@ -.& Ô@ 4 =$Å4 {@ *+XY @ " 4 ú TUVW # 4 12() n 4 OP>. lm, 1Ó&'; ±1) ú T UVW R Sï 4 ®3 ê OPY, Y 1d@ D EF#& -3 ç() Â >. ¢s£ *+ Ó; ù& /
(57) ú TUVW *+@ d;R Ø D l 16, ¢ jY æ; *+ Ó ;R & /
(58) é *+@ d;R åt- {|
(59) >. 1d@ Mannich*+D ortho : Z H I2() RaS 6-A&' ABC2() SïfP (6, ú TUVW R 789 :Y 4- G 6-A ù4 H NMR ÊËÌÍ4 ÿ¼ ®3 ê OP>.. , 4-methoxyphenol(1e)@ Mannich*+D 1Ó &'Y Sïft ¿¾(6, ÁY benzene $%ã& ' ])t ú TUVW # n4 OP>. s 1D 1e@ EF#;R 1d½> 1 2() uD ç& -36 þk)õ R 5>. Q# ç() ±1fY 3,5-dimethoxyphenol(1f)& D Ô@ morphorine4 *+,. ú TUVW # 11 ú TUVW # 12 1Ó&' nP>. , Ô@ -. & Ô@ morphorine paraformaldehyde 8 ' Mannich*+4 ; X, $% p-xylene4 =$r *+ Ó; ù()õ ú TUVW # 124 «D ¬) n4 OP(6 ú TUVW # D n4 §P>. Y 1f@ 4-AR Vµ -& @¼ sr O 8 *+ @ ¥ 8- {|() rS>. ortho ! "# . ortho AR T f8 OY # 1g~1j@ Mannich*+@ *+# *+ 78£Y :& ¼' ð½¾>(Table 3). 2-G 6A& o ³£ VW -R -. 1gG 1h @ TUVW Y Û< w Sïf8 Mannicho13Ä164 n4 OP>. ¢s£, HI2() p¹R º tert-butyl - ? OY 1i@ Mannich*+ D benzene£ ethanol$%&'Y 78£t ¿¾(6, ÁY n-buthanol$%&' Sïf8 # 17 (1d). 1. 2001, Vol. 45, No. 1. 59. 4 nP>. , 2,6-dimethoxyphenol(1j) morphorine @ one-pot Mannich*+()Y m íD ¬@ # 4 nY ¢ >. Y 1j@ qá X& @ »() ½6, *+ $% ethanol) 8 ² 19%t ¬ °
(60) !>. *+ 78£ Y :Y phenol@ ortho AR T f8 O8' phenol@ paraA&' 78">. Morphorine #& N-methylpiperazine4 () =$¼; *+X&Y º R §P>. ÞßX ݼ ½², phenol@ #;R *+# åS>Y ç4 N O(6 s =ÞD N-methoxymethyl ZI $ Mannich*+ n8S Þß X G Y *fY ç() % T >. $ %&' ( )* +,
(61) - . Table 4&'Y ´@ - Y ?:@ Mannich*+ X £àáP>. Hydroquinone(1k)@ Mannich*+ X, -@ ortho A(2-AG 5-A) &' TUVW *+ Sï # 214 nP( 6, TUVW *+ ú Sï # ; Ô n8$>. *², 2-methylresorcinol(1l)D -) 3¼ 4- G 6-A òR Z() Q# f 8 O?, phenol?: á@ 2-AR VW -) T f8 O8 =$ Mannich*+ X 4-G 6-A& ´@ TUVW-R # 22G 234 «D ¬) n4 OP>. .
(62) ! +,
(63) - . ?:R %, hydroxyquinoline naphtholD Mannich*+ ?:á@ D πx ë;) 3r EF# phenol½> ç( ) ±ÐfP(6, Þß X ±1) 90% 1@ D ¬) # 28Ä334 n4 OP>(Table 5). # 30@ ¬D *+$%) benzene4 =$Å 4 {Y 71%5(£, ethanol4 =$M()õ 99% t 7 OP>. # º $% =$Å4 { ¬ tY jY $%@ # å& /
(64) 8-hydroxyquinoline(1q)@ qá X@ " Ø - {|() Â >. 4-chloro-1-naphthol(1t)D x i -Y o ³R f8 O8 -.@ EF#;R Ø M() 1-naphthol(1r)4 =$Å4 { ½> Mannicho-@ ¬ &8$>. ! +,
(65) - azacrown ether 18. 11.
(66)
(67) . 60. . p¹R º azacrown ether 2dG 2e = $ Mannich*+D crown ether@ HI2 JK) 3r morphorine4 =$ *+½> ¬ Ø 5>(Table 6). lm, 3-hydroxypyridine(1a) Y 4hydroxyquinoline(1p) 1,4,7,10,13-pentaoxa-16-azacyclooctadecane(2d)@ Mannich*+ X ð½², ¬ 17%G 12%) <5>. XY azacrown ether@ HIJKG hydroxypyridineÁ@ 12() í D EF#;& -3 >. ¢s£ Q# º 3-methoxyphenol(1d)4 -.) ? azacrown ether () =$ Mannich*+D 1Ó&'; Z d;@ ¬ 4 ½r P>.. . rs Rt N¯°4 -.) =$? r-& paraformaldehyde ! "## $ %&' one-pot() Mannich*+4 , ¢ *+# ABC#4 ?¸ X, >ä D X'4 nP>. Hydroxypyridine4 -.) =$ Mannich*+ I) «D ¬@ Mannicho- n4 OP(6, methoxyphenol Y π-xR ·p naphtholj;I @ Mannich*+; º *+#4 £àáP>. lm, Q# º methoxyphenol4 -.) =$ Mannich *+D 1Ó&'; $w SïfP(6, ú T UVW # ; n4 OP>. ¢s£ azacrown ether () =$ Mannich*+D x*2() ¬ í¾(6, Y azacrown ether@ HIJK@ X) >. *+ 78£Y :Y ABC2 () -@ ortho Aù4 ®3Å(6, ( >0 ortho AR LY (, % 3-hydroxypyridine@ (&Y . )@ 2-A, 3-methoxyphenol@ (&Y 6-A&' *+ 78">. *|D 2000+
(68) !& @r
(69) fPä.. 1. (a) Blicke, B. B. Org. React. 1942, 1, 303. (b) Hellmann, H.; Opitz, G. Angew. Chem. 1956, 68, 265.. 2. (a) Tramontini, M. Synthesis 1973, 703. (b) Tramontini, M.; Angliolini, L. Tetrahedron 1990, 46, 1791. 3. (a) Evans, D. A.; Nelson, J. V.; Taber, T. R. Top Sterechem. 1982, 13, 1. (b) Cummings, T. F.; Shelton, J. R. J. Org. Chem. 1960, 25, 419. (c) House, H. O.; Trost, B. M.; J. Org. Chem. 1964, 29, 1339. (d) Tramontini, M.; Angliolini, L. Mannich Base: Chemistry and Uses; CRC Press: Boca Raton., 1994; pp 17-20. (e) Kuriakose, A. P. Indian J. Chem. 1975, 13, 1149. 4. Monti, S. A.; Johnson, W. O. Tetrahedron 1970, 26, 3685. 5. (a) Galantay, E.; Basco, I; Coombs, R. V. Synthesis 1974, 344. (b) Belikov, V. M.; Beloken, Y. D.; Dolgaya, M. M.; Martinkova, N. S. Tetrahedron 1970, 26, 1199. (c) Kurilo, G. N.; Rostova, N. I.; Grinev. A. N. Zh. Org. Khim. 1978, 14, 2627: Chem. Abstr. 1979, 90, 137616. (d) Ahn, J. S.; Harm, D. G.; Heaney, H.; Papageorgiou, G.; Willkins, R. F. Bull. Korean. Chem. Soc. 1994, 15(5), 329. (e) Mohrle, H.; Schnadel bach, D. Arch. Pharm. 1975, 308, 783. 6. (a) Rechert, B. ln Die Mannich Reaction; Springer Verlag: Berline, 1959. (b) Hellmann, H.; Opitz, G. In αAminoalkylierung; Verlag Chemie: Weiheim, 1960. (c) Hodgkin, J. H.; Allen, R, J. J. Macromol. Soc. Chem. 1977, AII, 937. 7. (a) Bogatsky, A. V.; Lukyanenko, N. G.; Pastushok, V. N.; Kostyanovsky, R. G. Synthesis 1983, 992. (b) Bogatsky, A. V.; Lukyanenko, N. G.; Pastushok, V. N.; Kostyanovsky, R. G. Chem. Abstra. 1982, 97, 216146c. (c) Lukyanenko, N. G.; Pastushok, V. N.; Bordunov, A. V. Synthesis 1991, 241. 8. (a) Chi, K.-W.; Wei, H.-C.; Kottke, T.; Lagow, R. J. J. Org. Chem. 1996, 61, 5684. (b) Su, N.; Bradshaw, J. S.; Savage, P. B.; Krakowiak, K. E.; Izatt, R. M.; Dewall, S. D.; Gokel, G. W. Tetrahedron 1999, 55, 9737. 9. (a) Sykes, P. A Guidebook to Mechanism in Organic Chemistry; 6th Ed.; Longman Scientific & Technical: New York, 1995; p 165. (b) Chi, K.-W.; Ahn, Y. S.; Shim, K. T.; Park, T. H.; Ahn J. S. Bull. Korean. Chem. Soc. 1999, 20(8), 973. 10. (a) Dyumaev, K. M.; Lokhov, R. E. Zh. Org. Khim. 1972, 416; Chem. Abstr. 1972, 76, 126728. (b) Gol’tsova, L. V.; Lezna, V. P.; Kuz’min, V. I.; Simrnov, L. D. Izv. Akad. Nauk SSSR Ser. Khim. 1984, 1660; Chem. Abstr. 1985, 102, 6156. 11. Habata, Y.; Saeki, T.; Watanabe, A.; Akabor, S.; Bradshaw, J. S. J. Heterocyclic Chem. 1999, 36, 355.. Journal of the Korean Chemical Society.
(70)
관련 문서
Secondary beginning teachers' views of scientific inquiry: with the view of Hands-on, Minds-on, and Hearts-on.. Introducing teaching STEAM as a practical
Secondary beginning teachers' views of scientific inquiry: with the view of Hands-on, Minds-on, and Hearts-on.. Introducing teaching STEAM as a practical
Secondary beginning teachers' views of scientific inquiry: with the view of Hands-on, Minds-on, and Hearts-on. Introducing teaching STEAM as a practical
Secondary beginning teachers' views of scientific inquiry: with the view of Hands-on, Minds-on, and Hearts-on.. Introducing teaching STEAM as a practical
Secondary beginning teachers' views of scientific inquiry: with the view of Hands-on, Minds-on, and Hearts-on.. Introducing teaching STEAM as a practical
20 6: enolate with ester using weaker bases ⇒ Aldol condensation. 20.6: enolate with ester
The goal of this study is to evaluate the self-management of gymnastic athletes in coping with condition of gymnastics competition depending on the
Fig. 2-53 Consolidation problem with two compressible strata. ⇒ Consolidation behavior of multilayered system depends on the relative values of k and m v for
